Major goals for this project are to establish the roles of Ang II and Na in resetting of the arterial baroreflex (ABR) in AngII-induced hypertension. Experiments will determine the integrative roles of the area postrema (AP), the paraventricular nucleus (PVN), and hepatoportal osmo/Na receptors in ABR resetting and the accompanying HT. The hypotheses to be tested are (1) HT due to low dose infusions of Ang II and NaCl involves an upward resetting of the ABR and (2) Converging projections from the AP, PVN, and hepatoportal osmo/Na receptors within the NTS determine the integrative neuronal response to baroreceptor afferent input. Both the resetting and changes in NTS neuronal responses involve activation in the AP and PVN. Activity within the AP is due to circulating Ang II, while the PVN is sensitive to Na. When Na is increased, hepatoportal reflexes will oppose ABR resetting and the Ang II-induced HT. To test these hypotheses, the combined and separate roles of AngII and Na on ABR control of RSNA, MAP and HT will be determined in conscious rats. Hepatoportal denervation, lesioning and AT1 receptor blockade of the AP and PVN, and selective activation of afferents in the three regions will be determined. One goal is to determine if AP and PVN inputs attenuate NTS neuronal responses to baroreceptor afferent inputs. Other goals are to determine if hepatoportal afferents facilitate baroreceptor-evoked single unit discharge, thereby opposing the inhibitory influence of AP and PVN inputs. Proposed studies are unique in that they are the first to investigate potential interactions between the brainstem (AP), descending hypothalamic (PVN) and ascending peripheral afferent (hepatoportal) inputs on the reflex regulation of sympathetic outflow and arterial pressure. Proposed studies will build upon our understanding of how circulating factors can influence the ABR and will provide a foundation for future studies to determine the specific neurotransmitter mechanisms that are active in modulating ABR function in health and disease.